Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments

Abstract

The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

We claim: 
     
         1 . An isolated recombinant antibody or antigen-binding fragment thereof that specifically binds to a coronavirus spike protein (CoV-S), wherein the antibody or antigen-binding fragment comprises:
 a heavy chain variable region (HCVR) comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3); and a light chain variable region (LCVR) comprising three light chain CDRs (LCDR1, LCDR2, and LCDR3);   wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprise, respectively, the amino acid sequences of:   SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 12, EVS, and SEQ ID NO: 16;   SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 32, EGN, and SEQ ID NO: 36;   SEQ ID NO: 44, SEQ ID NO: 26, SEQ ID NO: 47, SEQ ID NO: 51, EGN, and SEQ ID NO: 36;   SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 51, EGT, and SEQ ID NO: 36;   SEQ ID NO: 76, SEQ ID NO: 78, SEQ ID NO: 80, SEQ ID NO: 84, EDS, and SEQ ID NO: 88;   SEQ ID NO: 96, SEQ ID NO: 98, SEQ ID NO: 100, SEQ ID NO: 104, AAS, and SEQ ID NO: 108;   SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO: 120, SEQ ID NO: 124, GAS, and SEQ ID NO: 128;   SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 144, GAS, and SEQ ID NO: 146;   SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 158, SEQ ID NO: 162, GNS, and SEQ ID NO: 166;   SEQ ID NO: 174, SEQ ID NO: 176, SEQ ID NO: 178, SEQ ID NO: 182, SND, and SEQ ID NO: 186;   SEQ ID NO: 194, SEQ ID NO: 196, SEQ ID NO: 198, SEQ ID NO: 202, DND, and SEQ ID NO: 206;   SEQ ID NO: 214, SEQ ID NO: 216, SEQ ID NO: 218, SEQ ID NO: 222, GAS, and SEQ ID NO: 224;   SEQ ID NO: 232, SEQ ID NO: 234, SEQ ID NO: 236, SEQ ID NO: 240, DAS, and SEQ ID NO: 244;   SEQ ID NO: 252, SEQ ID NO: 254, SEQ ID NO: 256, SEQ ID NO: 260, GAT, and SEQ ID NO: 264;   SEQ ID NO: 272, SEQ ID NO: 274, SEQ ID NO: 276, SEQ ID NO: 280, AAS, and SEQ ID NO: 282;   SEQ ID NO: 290, SEQ ID NO: 292, SEQ ID NO: 294, SEQ ID NO: 298, SDN, and SEQ ID NO: 302;   SEQ ID NO: 310, SEQ ID NO: 312, SEQ ID NO: 314, SEQ ID NO: 318, VNN, and SEQ ID NO: 322;   SEQ ID NO: 330, SEQ ID NO: 332, SEQ ID NO: 334, SEQ ID NO: 338, AAS, and SEQ ID NO: 340;   SEQ ID NO: 96, SEQ ID NO: 98, SEQ ID NO: 350, SEQ ID NO: 354, AAS, and SEQ ID NO: 356;   SEQ ID NO: 364, SEQ ID NO: 366, SEQ ID NO: 368, SEQ ID NO: 372, AAS, and SEQ ID NO: 374;   SEQ ID NO: 382, SEQ ID NO: 384, SEQ ID NO: 386, SEQ ID NO: 390, KAS, and SEQ ID NO: 394;   SEQ ID NO: 402, SEQ ID NO: 98, SEQ ID NO: 405, SEQ ID NO: 409, DAS, and SEQ ID NO: 411;   SEQ ID NO: 419, SEQ ID NO: 421, SEQ ID NO: 423, SEQ ID NO: 427, EVS, and SEQ ID NO: 429;   SEQ ID NO: 437, SEQ ID NO: 138, SEQ ID NO: 440, SEQ ID NO: 444, DKN, and SEQ ID NO: 448;   SEQ ID NO: 456, SEQ ID NO: 458, SEQ ID NO: 460, SEQ ID NO: 84, ELT, and SEQ ID NO: 467;   SEQ ID NO: 475, SEQ ID NO: 477, SEQ ID NO: 479, SEQ ID NO: 483, DVT, and SEQ ID NO: 487;   SEQ ID NO: 495, SEQ ID NO: 497, SEQ ID NO: 499, SEQ ID NO: 503, EVT, and SEQ ID NO: 507;   SEQ ID NO: 515, SEQ ID NO: 517, SEQ ID NO: 519, SEQ ID NO: 523, EGS, and SEQ ID NO: 36;   SEQ ID NO: 533, SEQ ID NO: 535, SEQ ID NO: 537, SEQ ID NO: 483, DVS, and SEQ ID NO: 544;   SEQ ID NO: 552, SEQ ID NO: 554, SEQ ID NO: 556, SEQ ID NO: 84, EVS, and SEQ ID NO: 560;   SEQ ID NO: 568, SEQ ID NO: 570, SEQ ID NO: 572, SEQ ID NO: 576, ENN, and SEQ ID NO: 580;   SEQ ID NO: 588, SEQ ID NO: 590, SEQ ID NO: 592, SEQ ID NO: 596, GAS, and SEQ ID NO: 598;   SEQ ID NO: 606, SEQ ID NO: 608, SEQ ID NO: 610, SEQ ID NO: 614, GAS, and SEQ ID NO: 616;   SEQ ID NO: 624, SEQ ID NO: 626, SEQ ID NO: 628, SEQ ID NO: 632, LGS, and SEQ ID NO: 636;   SEQ ID NO: 644, SEQ ID NO: 646, SEQ ID NO: 648, SEQ ID NO: 652, LGS, and SEQ ID NO: 655;   SEQ ID NO: 663, SEQ ID NO: 665, SEQ ID NO: 667, SEQ ID NO: 124, GAS, and SEQ ID NO: 671;   SEQ ID NO: 679, SEQ ID NO: 78, SEQ ID NO: 682, SEQ ID NO: 686, GAS, and SEQ ID NO: 688;   SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 704, SAS, and SEQ ID NO: 708;   SEQ ID NO: 696, SEQ ID NO: 716, SEQ ID NO: 718, SEQ ID NO: 722, GAS, and SEQ ID NO: 724;   SEQ ID NO: 732, SEQ ID NO: 734, SEQ ID NO: 736, SEQ ID NO: 740, AAS, and SEQ ID NO: 742;   SEQ ID NO: 750, SEQ ID NO: 497, SEQ ID NO: 752, SEQ ID NO: 756, EVT, and SEQ ID NO: 758;   SEQ ID NO: 766, SEQ ID NO: 768, SEQ ID NO: 770, SEQ ID NO: 774, KDS, and SEQ ID NO: 778;   SEQ ID NO: 786, SEQ ID NO: 788, SEQ ID NO: 790, SEQ ID NO: 794, GNT, and SEQ ID NO: 798;   SEQ ID NO: 806, SEQ ID NO: 497, SEQ ID NO: 808, SEQ ID NO: 812, EVT, and SEQ ID NO: 814;   SEQ ID NO: 822, SEQ ID NO: 497, SEQ ID NO: 825, SEQ ID NO: 756, EVS, and SEQ ID NO: 829;   SEQ ID NO: 837, SEQ ID NO: 839, SEQ ID NO: 841, SEQ ID NO: 845, KIS, and SEQ ID NO: 849;   SEQ ID NO: 857, SEQ ID NO: 859, SEQ ID NO: 861, SEQ ID NO: 865, AAS, and SEQ ID NO: 867;   SEQ ID NO: 76, SEQ ID NO: 876, SEQ ID NO: 878, SEQ ID NO: 84, EDS, and SEQ ID NO: 36;   SEQ ID NO: 889, SEQ ID NO: 891, SEQ ID NO: 893, SEQ ID NO: 897, GNS, and SEQ ID NO: 899;   SEQ ID NO: 154, SEQ ID NO: 908, SEQ ID NO: 910, SEQ ID NO: 914, GHT, and SEQ ID NO: 166;   SEQ ID NO: 924, SEQ ID NO: 926, SEQ ID NO: 928, SEQ ID NO: 576, RNN, and SEQ ID NO: 935;   SEQ ID NO: 943, SEQ ID NO: 945, SEQ ID NO: 947, SEQ ID NO: 951, LGS, and SEQ ID NO: 655;   SEQ ID NO: 959, SEQ ID NO: 961, SEQ ID NO: 963, SEQ ID NO: 967, WAS, and SEQ ID NO: 971;   SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 704, SAS, and SEQ ID NO: 979;   SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 704, SAS, and SEQ ID NO: 985; or   SEQ ID NO: 991, SEQ ID NO: 993, SEQ ID NO: 995, SEQ ID NO: 999, GAS, and SEQ ID NO: 1003.   
     
     
         2 . The antibody or antigen-binding fragment of  claim 1 , wherein the antibody or antigen-binding fragment has one or more of the following characteristics:
 (a) binds to CoV-S with an EC 50  of less than about 10 −8  M; and/or   (b) demonstrates an increase in survival in a coronavirus-infected animal after administration to said coronavirus-infected animal, as compared to a comparable coronavirus-infected animal without said administration.   
     
     
         3 . The antibody or antigen-binding fragment of  claim 1 , wherein the HCVR and the LCVR comprise, respectively, the amino acid sequences selected from the group consisting of SEQ ID NOs: 2 and 10; 22 and 30; 42 and 49; 58 and 66; 74 and 82; 94 and 102; 114 and 122; 134 and 142; 152 and 160; 172 and 180; 192 and 200; 212 and 220; 230 and 238; 250 and 258; 270 and 278; 288 and 296; 308 and 316; 328 and 336; 346 and 352; 362 and 370; 380 and 388; 400 and 407; 417 and 425; 435 and 442; 454 and 462; 473 and 481; 493 and 501; 513 and 521; 531 and 539; 550 and 558; 566 and 574; 586 and 594; 604 and 612; 622 and 630; 642 and 650; 661 and 669; 677 and 684; 694 and 702; 714 and 720; 730 and 738; 748 and 754; 764 and 772; 784 and 792; 804 and 810; 820 and 827; 835 and 843; 855 and 863; 873 and 880; 887 and 895; 905 and 912; 922 and 930; 941 and 949; 957 and 965; 694 and 977; 694 and 983; and 989 and 997. 
     
     
         4 . The antibody or antigen-binding fragment of  claim 1 , which is an antibody comprising a heavy chain and a light chain, wherein the heavy chain (HC) and the light chain (LC) comprise, respectively, the amino acid sequences selected from the group consisting of SEQ ID NOs: 18 and 20; 38 and 40; 54 and 56; 70 and 72; 90 and 92; 110 and 112; 130 and 132; 148 and 150; 168 and 170; 188 and 190; 208 and 210; 226 and 228; 246 and 248; 266 and 268; 284 and 286; 304 and 306; 324 and 326; 342 and 344; 358 and 360; 376 and 378; 396 and 398; 413 and 415; 431 and 433; 450 and 452; 469 and 471; 489 and 491; 509 and 511; 527 and 529; 546 and 548; 562 and 564; 582 and 584; 600 and 602; 618 and 620; 638 and 640; 657 and 659; 673 and 675; 690 and 692; 710 and 712; 726 and 728; 744 and 746; 760 and 762; 780 and 782; 800 and 802; 816 and 818; 831 and 833; 851 and 853; 869 and 871; 883 and 885; 901 and 903; 918 and 920; 937 and 939; 953 and 955; 973 and 975; 710 and 981; 710 and 987; 1005 and 1007; 1075 and 511; and 1077 and 378. 
     
     
         5 . An antibody or antigen-binding fragment thereof that competes with the antibody or antigen-binding fragment of  claim 1  for binding to CoV-S, or that binds to the same epitope as, or to an overlapping epitope on, CoV-S as the antibody or antigen-binding fragment of  claim 1 . 
     
     
         6 . The antibody or antigen-binding fragment of  claim 1 , which:
 (i) is multispecific;   (ii) comprises one or more of the following properties:
 (a) inhibits growth of coronavirus; 
 (b) binds to the surface of a coronavirus; 
 (c) limits spread of coronavirus infection of cells in vitro; and 
 (d) protects mice engineered to express the human ACE2 or TMPRSS2 protein from death and/or weight loss caused by coronavirus infection; and/or 
   (iii) is an antibody or antigen-binding fragment wherein said CoV-S is SARS-COV-2-S.   
     
     
         7 . A polynucleotide encoding:
 (a) an antibody or antigen-binding fragment thereof of  claim 1 ;   (b) a HCVR and a LCVR comprising the HCVR and LCVR sequences, respectively, selected from the group consisting of SEQ ID NOs: 2 and 10; 22 and 30; 42 and 49; 58 and 66; 74 and 82; 94 and 102; 114 and 122; 134 and 142; 152 and 160; 172 and 180; 192 and 200; 212 and 220; 230 and 238; 250 and 258; 270 and 278; 288 and 296; 308 and 316; 328 and 336; 346 and 352; 362 and 370; 380 and 388; 400 and 407; 417 and 425; 435 and 442; 454 and 462; 473 and 481; 493 and 501; 513 and 521; 531 and 539; 550 and 558; 566 and 574; 586 and 594; 604 and 612; 622 and 630; 642 and 650; 661 and 669; 677 and 684; 694 and 702; 714 and 720; 730 and 738; 748 and 754; 764 and 772; 784 and 792; 804 and 810; 820 and 827; 835 and 843; 855 and 863; 873 and 880; 887 and 895; 905 and 912; 922 and 930; 941 and 949; 957 and 965; 694 and 977; 694 and 983; and 989 and 997; or   (c) a heavy chain (HC) and a light chain (LC) comprising the HC and LC sequences, respectively, selected from the group consisting of SEQ ID NOs: 18 and 20; 38 and 40; 54 and 56; 70 and 72; 90 and 92; 110 and 112; 130 and 132; 148 and 150; 168 and 170; 188 and 190; 208 and 210; 226 and 228; 246 and 248; 266 and 268; 284 and 286; 304 and 306; 324 and 326; 342 and 344; 358 and 360; 376 and 378; 396 and 398; 413 and 415; 431 and 433; 450 and 452; 469 and 471; 489 and 491; 509 and 511; 527 and 529; 546 and 548; 562 and 564; 582 and 584; 600 and 602; 618 and 620; 638 and 640; 657 and 659; 673 and 675; 690 and 692; 710 and 712; 726 and 728; 744 and 746; 760 and 762; 780 and 782; 800 and 802; 816 and 818; 831 and 833; 851 and 853; 869 and 871; 883 and 885; 901 and 903; 918 and 920; 937 and 939; 953 and 955; 973 and 975; 710 and 981; 710 and 987; 1005 and 1007; 1075 and 511; and 1077 and 378.   
     
     
         8 . A vector comprising the polynucleotide of  claim 7 . 
     
     
         9 . An isolated host cell comprising the antibody or antigen-binding fragment of  claim 1 . 
     
     
         10 . A pair of polynucleotides, wherein:
 (a) the first polynucleotide encodes a heavy chain variable region (HCVR) comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3), and the second polynucleotide encodes a light chain variable region (LCVR) comprising three light chain CDRs (LCDR1, LCDR2, and LCDR3), wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprise, respectively, the amino acid sequences of:   SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 12, EVS, and SEQ ID NO: 16;   SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 32, EGN, and SEQ ID NO: 36;   SEQ ID NO: 44, SEQ ID NO: 26, SEQ ID NO: 47, SEQ ID NO: 51, EGN, and SEQ ID NO: 36;   SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 51, EGT, and SEQ ID NO: 36;   SEQ ID NO: 76, SEQ ID NO: 78, SEQ ID NO: 80, SEQ ID NO: 84, EDS, and SEQ ID NO: 88;   SEQ ID NO: 96, SEQ ID NO: 98, SEQ ID NO: 100, SEQ ID NO: 104, AAS, and SEQ ID NO: 108;   SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO: 120, SEQ ID NO: 124, GAS, and SEQ ID NO: 128;   SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 144, GAS, and SEQ ID NO: 146;   SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 158, SEQ ID NO: 162, GNS, and SEQ ID NO: 166;   SEQ ID NO: 174, SEQ ID NO: 176, SEQ ID NO: 178, SEQ ID NO: 182, SND, and SEQ ID NO: 186;   SEQ ID NO: 194, SEQ ID NO: 196, SEQ ID NO: 198, SEQ ID NO: 202, DND, and SEQ ID NO: 206;   SEQ ID NO: 214, SEQ ID NO: 216, SEQ ID NO: 218, SEQ ID NO: 222, GAS, and SEQ ID NO: 224;   SEQ ID NO: 232, SEQ ID NO: 234, SEQ ID NO: 236, SEQ ID NO: 240, DAS, and SEQ ID NO: 244;   SEQ ID NO: 252, SEQ ID NO: 254, SEQ ID NO: 256, SEQ ID NO: 260, GAT, and SEQ ID NO: 264;   SEQ ID NO: 272, SEQ ID NO: 274, SEQ ID NO: 276, SEQ ID NO: 280, AAS, and SEQ ID NO: 282;   SEQ ID NO: 290, SEQ ID NO: 292, SEQ ID NO: 294, SEQ ID NO: 298, SDN, and SEQ ID NO: 302;   SEQ ID NO: 310, SEQ ID NO: 312, SEQ ID NO: 314, SEQ ID NO: 318, VNN, and SEQ ID NO: 322;   SEQ ID NO: 330, SEQ ID NO: 332, SEQ ID NO: 334, SEQ ID NO: 338, AAS, and SEQ ID NO: 340;   SEQ ID NO: 96, SEQ ID NO: 98, SEQ ID NO: 350, SEQ ID NO: 354, AAS, and SEQ ID NO: 356;   SEQ ID NO: 364, SEQ ID NO: 366, SEQ ID NO: 368, SEQ ID NO: 372, AAS, and SEQ ID NO: 374;   SEQ ID NO: 382, SEQ ID NO: 384, SEQ ID NO: 386, SEQ ID NO: 390, KAS, and SEQ ID NO: 394;   SEQ ID NO: 402, SEQ ID NO: 98, SEQ ID NO: 405, SEQ ID NO: 409, DAS, and SEQ ID NO: 411;   SEQ ID NO: 419, SEQ ID NO: 421, SEQ ID NO: 423, SEQ ID NO: 427, EVS, and SEQ ID NO: 429;   SEQ ID NO: 437, SEQ ID NO: 138, SEQ ID NO: 440, SEQ ID NO: 444, DKN, and SEQ ID NO: 448;   SEQ ID NO: 456, SEQ ID NO: 458, SEQ ID NO: 460, SEQ ID NO: 84, ELT, and SEQ ID NO: 467;   SEQ ID NO: 475, SEQ ID NO: 477, SEQ ID NO: 479, SEQ ID NO: 483, DVT, and SEQ ID NO: 487;   SEQ ID NO: 495, SEQ ID NO: 497, SEQ ID NO: 499, SEQ ID NO: 503, EVT, and SEQ ID NO: 507;   SEQ ID NO: 515, SEQ ID NO: 517, SEQ ID NO: 519, SEQ ID NO: 523, EGS, and SEQ ID NO: 36;   SEQ ID NO: 533, SEQ ID NO: 535, SEQ ID NO: 537, SEQ ID NO: 483, DVS, and SEQ ID NO: 544;   SEQ ID NO: 552, SEQ ID NO: 554, SEQ ID NO: 556, SEQ ID NO: 84, EVS, and SEQ ID NO: 560;   SEQ ID NO: 568, SEQ ID NO: 570, SEQ ID NO: 572, SEQ ID NO: 576, ENN, and SEQ ID NO: 580;   SEQ ID NO: 588, SEQ ID NO: 590, SEQ ID NO: 592, SEQ ID NO: 596, GAS, and SEQ ID NO: 598;   SEQ ID NO: 606, SEQ ID NO: 608, SEQ ID NO: 610, SEQ ID NO: 614, GAS, and SEQ ID NO: 616;   SEQ ID NO: 624, SEQ ID NO: 626, SEQ ID NO: 628, SEQ ID NO: 632, LGS, and SEQ ID NO: 636;   SEQ ID NO: 644, SEQ ID NO: 646, SEQ ID NO: 648, SEQ ID NO: 652, LGS, and SEQ ID NO: 655;   SEQ ID NO: 663, SEQ ID NO: 665, SEQ ID NO: 667, SEQ ID NO: 124, GAS, and SEQ ID NO: 671;   SEQ ID NO: 679, SEQ ID NO: 78, SEQ ID NO: 682, SEQ ID NO: 686, GAS, and SEQ ID NO: 688;   SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 704, SAS, and SEQ ID NO: 708;   SEQ ID NO: 696, SEQ ID NO: 716, SEQ ID NO: 718, SEQ ID NO: 722, GAS, and SEQ ID NO: 724;   SEQ ID NO: 732, SEQ ID NO: 734, SEQ ID NO: 736, SEQ ID NO: 740, AAS, and SEQ ID NO: 742;   SEQ ID NO: 750, SEQ ID NO: 497, SEQ ID NO: 752, SEQ ID NO: 756, EVT, and SEQ ID NO: 758;   SEQ ID NO: 766, SEQ ID NO: 768, SEQ ID NO: 770, SEQ ID NO: 774, KDS, and SEQ ID NO: 778;   SEQ ID NO: 786, SEQ ID NO: 788, SEQ ID NO: 790, SEQ ID NO: 794, GNT, and SEQ ID NO: 798;   SEQ ID NO: 806, SEQ ID NO: 497, SEQ ID NO: 808, SEQ ID NO: 812, EVT, and SEQ ID NO: 814;   SEQ ID NO: 822, SEQ ID NO: 497, SEQ ID NO: 825, SEQ ID NO: 756, EVS, and SEQ ID NO: 829;   SEQ ID NO: 837, SEQ ID NO: 839, SEQ ID NO: 841, SEQ ID NO: 845, KIS, and SEQ ID NO: 849;   SEQ ID NO: 857, SEQ ID NO: 859, SEQ ID NO: 861, SEQ ID NO: 865, AAS, and SEQ ID NO: 867;   SEQ ID NO: 76, SEQ ID NO: 876, SEQ ID NO: 878, SEQ ID NO: 84, EDS, and SEQ ID NO: 36;   SEQ ID NO: 889, SEQ ID NO: 891, SEQ ID NO: 893, SEQ ID NO: 897, GNS, and SEQ ID NO: 899;   SEQ ID NO: 154, SEQ ID NO: 908, SEQ ID NO: 910, SEQ ID NO: 914, GHT, and SEQ ID NO: 166;   SEQ ID NO: 924, SEQ ID NO: 926, SEQ ID NO: 928, SEQ ID NO: 576, RNN, and SEQ ID NO: 935;   SEQ ID NO: 943, SEQ ID NO: 945, SEQ ID NO: 947, SEQ ID NO: 951, LGS, and SEQ ID NO: 655;   SEQ ID NO: 959, SEQ ID NO: 961, SEQ ID NO: 963, SEQ ID NO: 967, WAS, and SEQ ID NO: 971;   SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 704, SAS, and SEQ ID NO: 979;   SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 704, SAS, and SEQ ID NO: 985; or   SEQ ID NO: 991, SEQ ID NO: 993, SEQ ID NO: 995, SEQ ID NO: 999, GAS, and SEQ ID NO: 1003;   (b) the first polynucleotide encodes a HCVR, and the second polynucleotide encodes a LCVR, wherein the HCVR and the LCVR comprise, respectively, the amino acid sequences of SEQ ID NOs: 2 and 10; 22 and 30; 42 and 49; 58 and 66; 74 and 82; 94 and 102; 114 and 122; 134 and 142; 152 and 160; 172 and 180; 192 and 200; 212 and 220; 230 and 238; 250 and 258; 270 and 278; 288 and 296; 308 and 316; 328 and 336; 346 and 352; 362 and 370; 380 and 388; 400 and 407; 417 and 425; 435 and 442; 454 and 462; 473 and 481; 493 and 501; 513 and 521; 531 and 539; 550 and 558; 566 and 574; 586 and 594; 604 and 612; 622 and 630; 642 and 650; 661 and 669; 677 and 684; 694 and 702; 714 and 720; 730 and 738; 748 and 754; 764 and 772; 784 and 792; 804 and 810; 820 and 827; 835 and 843; 855 and 863; 873 and 880; 887 and 895; 905 and 912; 922 and 930; 941 and 949; 957 and 965; 694 and 977; 694 and 983; or 989 and 997; or   (c) the first polynucleotide a heavy chain, and the second polynucleotide encodes a light chain, wherein the heavy chain and the light chain comprise, respectively, the amino acid sequences of SEQ ID NOs: 18 and 20; 38 and 40; 54 and 56; 70 and 72; 90 and 92; 110 and 112; 130 and 132; 148 and 150; 168 and 170; 188 and 190; 208 and 210; 226 and 228; 246 and 248; 266 and 268; 284 and 286; 304 and 306; 324 and 326; 342 and 344; 358 and 360; 376 and 378; 396 and 398; 413 and 415; 431 and 433; 450 and 452; 469 and 471; 489 and 491; 509 and 511; 527 and 529; 546 and 548; 562 and 564; 582 and 584; 600 and 602; 618 and 620; 638 and 640; 657 and 659; 673 and 675; 690 and 692; 710 and 712; 726 and 728; 744 and 746; 760 and 762; 780 and 782; 800 and 802; 816 and 818; 831 and 833; 851 and 853; 869 and 871; 883 and 885; 901 and 903; 918 and 920; 937 and 939; 953 and 955; 973 and 975; 710 and 981; 710 and 987; 1005 and 1007; 1075 and 511; or 1077 and 378.   
     
     
         11 . A composition or kit comprising the antibody or antigen-binding fragment of  claim 1  and a further therapeutic agent, or a pharmaceutical composition comprising the antibody or antigen-binding fragment of  claim 1  and pharmaceutically acceptable carrier and, optionally, a further therapeutic agent. 
     
     
         12 . A vessel or injection device comprising the antibody or antigen-binding fragment of  claim 1 . 
     
     
         13 . The antibody or antigen-binding fragment thereof of  claim 1  that (a) neutralizes an omicron variant of SARS-COV-2, or (b) neutralizes an omicron variant selected from BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, or BA.4/BA.5. 
     
     
         14 . The antibody or antigen-binding fragment of  claim 1  comprising a heavy chain constant region with 252Y, 254T and 256E modifications. 
     
     
         15 . A pair of vectors comprising, respectively, the first polynucleotide and the second polynucleotide of  claim 10 . 
     
     
         16 . An isolated host cell comprising the pair of polynucleotides of  claim 10 . 
     
     
         17 . An isolated host cell comprising the pair of vectors of  claim 15 . 
     
     
         18 . An isolated host cell comprising the polynucleotide of  claim 7 . 
     
     
         19 . An isolated host cell comprising the vector of  claim 8 . 
     
     
         20 . An isolated host cell comprising the antibody or antigen-binding fragment of  claim 3 .